Adsorptive Granulocyte/Monocyte Apheresis for the Maintenance of Remission in Patients with Ulcerative Colitis: A Prospective Randomized, Double Blind, Sham-Controlled Clinical Trial

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.

Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn's Disease

BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

Cytapheresis in Patients with Severe Ulcerative Colitis after Failure of Intravenous Corticosteroid: A Long-Term Retrospective Cohort Study

BACKGROUND/AIMS: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. METHODS: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of > or =7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. RESULTS: CAP induced clinical remission (CAI or =12, n=25) than for moderately severe UC at entry (7< or =CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. CONCLUSIONS: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.